The grant's purpose was to examine the endogenous mechanisms pain perception, employing as a model system the observation that acute exposure to stressful events induced analgesia. A wide range of stressors display this capability, and also exhibit adaptation to the analgesic response to chronic exposure. In examining the mechanisms subserving stress-induced analgesia, it was observed that qualitatively different stressors show full and reciprocal cross-tolerance. While some stressors such as glucoprivation develop cross-tolerance and synergy with morphine, others such as swim do not. Moreover, naloxone, a potent opiate antigonist, fails to block the analgesic effect of both stressors, indicating that some stressors appear to act independently of the endogenous opiate systems while others appear to interact partially with it. Further studies investigating non-opioid mechanisms in pain-inhibition have shown that the pituitary, particularly its anterior lobe, as well as the medial-basal hypothalamus are integral for the full expression of the analgesic responses to non-opioid stressors. Yet morphine analgesia is impaired minimally following these hypothalamo-hypophyseal manipulations. Further work is being carried out to characterize non-opioid pathways in pain-inhibition and may be an alternate source of analgesic compounds without addictive liability.